Increased thrombin-activatable fibrinolysis inhibitor and decreased tissue factor pathway inhibitor in patients with hypothyroidism

Abstract

Various abnormalities of coagulation-fibrinolytic system have been reported in patients with thyroid dysfunction. Several studies indicate that coagulation and fibrinolytic system is disturbed in the patients with hypothyroidism. Also, the influence of hypothyroidism on hemostasis is controversial; both hypocoagulable and hypercoagulable states have been reported. The levels of plasma thrombin-activatable fibrinolysis inhibitor (TAFI) antigen and tissue factor pathway inhibitor (TFPI) have been investigated only once in patients with hypothyroidism. Therefore, the main purpose of this study was to evaluate the profile of coagulation and fibrinolytic parameters including TAFI and TFPI in patients with hypothyroidism. Fifteen patients with untreated hypothyroidism and 15 age-matched healthy controls were included in the study. Factors V(FV), VII (FVII), VIII (FVIII) activities, von Willebrand factor (vWF), protein C, protein S, thrombomodulin (TM), TFPI, and TAFI were measured. The relationships between serum thyroid hormones and these hemostatic parameters were examined. Compared with the control subjects, FVII activity, and TM Ag and TAFI Ag levels were significantly increased in patients with hypothyroidism, whereas FV, FVIII, vWF, protein C and protein S activities, and TFPI Ag levels were significantly decreased. We did not find any significant correlation between serum thyroid hormones and the hemostatic parameters that we measured. In conclusion, we found some important differences in the hemostatic parameters between the patients with hypothyroidism and healthy controls. Increased FVII, TM, and TAFI and decreased FV, FVIII, vWF, protein C, protein S, and TFPI in these patients represent a potential hypercoagulable and hypofibrinolytic state, possible endothelial dysfunction, which might augment the risk for atherosclerotic and atherothrombotic complications. Thus, disturbances of the hemostatic system may contribute to the excess mortality due to cardiovascular disease seen in patients with hypothyroidism.

Increased thrombin-activatable fibrinolysis inhibitor and decreased tissue factor pathway inhibitor in patients with hyperthyroidism

“…Interestingly, we very recently demonstrated a quite similar hypercoagulative status in hypothyroid patients (decreased TFPI and increased TAFI) [43]. A cause of the analogies between the results obtained in the two studies is not clear.…”

Coagulation and fibrinolysis in thyroid dysfunction

“…TAFI : [45,46] N normal, vWD von Willebrand Disease, TF tissue factor, PT prothrombin time, aPTT activated partial thromboplastin time, : increased, ; decreased, = the change is not significant : increased, ; decreased, = the change is not significant…”

“…In two different studies that we have conducted, an increase in fibrinogen, FVII, PAI-1, AT III, TM, and TAFI, and a decrease in FV, FVIII, vWF, protein C, protein S, and TFPI was determined in patients with newly diagnosed and untreated hypothyroidism compared to the control group. As a consequence, it was suggested that these changes might indicate endothelium dysfunction, hypofibrinolysis, and hypercoagulability rather than a tendency toward bleeding; thus, might lead to an increase in the risk for thrombosis [5,46].…”

Circulating MiR-146a May be a Potential Biomarker of Coronary Heart Disease in Patients with Subclinical Hypothyroidism

“…Most studies have suggested that patients with SCH have abnormal blood lipid levels, which may accelerate atherosclerosis [39-41]. It has also been proposed that the coagulation and fibrinolytic systems are disturbed in patients with SCH [42, 43]. Moreover, patients with SCH tended to exhibit increased platelet activation and platelet activity which enhances the risk of atherothrombosis in CHD [44].…”